Details of the Drug Combination

General Information of Drug Combination (ID: DC4NM7D)

Drug Combination Name

Bosentan Terameprocol

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Bosentan DMIOGBU

Terameprocol DMC3P45

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 3.77

Bliss Independence Score: 3.77

Loewe Additivity Score: 9.26

LHighest Single Agent (HSA) Score: 9.26

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Bosentan

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[2]
Pulmonary hypertension	BB01	Approved	[3]
Scleroderma	4A42	Investigative	[3]

Bosentan Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Modulator	[6]
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Modulator	[6]
------------------------------------------------------------------------------------

Bosentan Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[7]
------------------------------------------------------------------------------------

Bosentan Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]
------------------------------------------------------------------------------------

Bosentan Interacts with 40 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Decreases Expression	[5]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Expression	[5]
Serine/threonine-protein kinase DCLK1 (DCLK1)	OTVSPS98	DCLK1_HUMAN	Affects Expression	[5]
Kynurenine 3-monooxygenase (KMO)	OT3MRMM9	KMO_HUMAN	Affects Expression	[5]
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Affects Expression	[5]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Decreases Expression	[5]
Alcohol dehydrogenase 1C (ADH1C)	OTO1DV7F	ADH1G_HUMAN	Decreases Expression	[5]
Complement component C9 (C9)	OT7I5FDX	CO9_HUMAN	Affects Expression	[5]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[5]
Fructose-bisphosphate aldolase B (ALDOB)	OT7FR69A	ALDOB_HUMAN	Decreases Expression	[5]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Increases Expression	[5]
All-trans-retinol dehydrogenase ADH4 (ADH4)	OTKDKKNG	ADH4_HUMAN	Decreases Expression	[5]
Glutathione S-transferase theta-2 (GSTT2)	OTANW3TJ	GST2_HUMAN	Decreases Expression	[5]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[5]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)	OTNAZVKB	3BHS1_HUMAN	Affects Expression	[5]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Affects Expression	[5]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[5]
Macrophage mannose receptor 1 (MRC1)	OTTVCOPT	MRC1_HUMAN	Affects Expression	[5]
G0/G1 switch protein 2 (G0S2)	OT8FL49L	G0S2_HUMAN	Affects Expression	[5]
Carbamoyl-phosphate synthase , mitochondrial (CPS1)	OTXV8NSR	CPSM_HUMAN	Decreases Expression	[5]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Affects Expression	[5]
Achaete-scute homolog 1 (ASCL1)	OTI4X44G	ASCL1_HUMAN	Affects Expression	[5]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Decreases Expression	[5]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Affects Expression	[5]
Metallothionein-1X (MT1X)	OT9AKFVS	MT1X_HUMAN	Increases Expression	[5]
Complement factor H-related protein 3 (CFHR3)	OTYL8SDO	FHR3_HUMAN	Affects Expression	[5]
Nuclear factor 1 X-type (NFIX)	OT1DPZAE	NFIX_HUMAN	Decreases Expression	[5]
Phosphoenolpyruvate carboxykinase , mitochondrial (PCK2)	OTJ8LX4N	PCKGM_HUMAN	Decreases Expression	[5]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[5]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[5]
Liver-expressed antimicrobial peptide 2 (LEAP2)	OTUOPIS5	LEAP2_HUMAN	Affects Expression	[5]
N-acetylmuramoyl-L-alanine amidase (PGLYRP2)	OTF8319A	PGRP2_HUMAN	Affects Expression	[5]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[5]
Normal mucosa of esophagus-specific gene 1 protein (C15ORF48)	OT85J32K	NMES1_HUMAN	Affects Expression	[5]
ATP-binding cassette sub-family G member 5 (ABCG5)	OT1OMY93	ABCG5_HUMAN	Affects Expression	[5]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Decreases Expression	[5]
Solute carrier family 22 member 7 (SLC22A7)	OTKTNH1W	S22A7_HUMAN	Affects Expression	[5]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Decreases Expression	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[10]
Coxsackievirus and adenovirus receptor (CXADR)	OT9ZP02A	CXAR_HUMAN	Decreases Expression	[11]
------------------------------------------------------------------------------------


⏷ Show the Full List of 40 DOT(s)

Indication(s) of Terameprocol

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]

Terameprocol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Transcription factor Sp1 (SP1)	TTZEP6S	SP1_HUMAN	Modulator	[4]
------------------------------------------------------------------------------------

References

1	CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3494).
3	Bosentan FDA Label
4	Terameprocol, a novel site-specific transcription inhibitor with anticancer activity. IDrugs. 2008 Mar;11(3):204-14.
5	Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7	Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
8	Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
9	Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301.
10	From the Cover: MechanisticInsights in Cytotoxic and Cholestatic Potential of the Endothelial Receptor Antagonists Using HepaRG Cells. Toxicol Sci. 2017 Jun 1;157(2):451-464. doi: 10.1093/toxsci/kfx062.
11	Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. J Gen Virol. 2010 Aug;91(Pt 8):1959-1970. doi: 10.1099/vir.0.020065-0. Epub 2010 Apr 14.